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Biomedical subjects

J A Walker-Smith

Publications and source records attributed to J A Walker-Smith.

At least 19 recordsLinked to original sources
PubMed1992

Tomlinson report.

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Health Facility Closure↗
PubMed1992

Cow milk-sensitive enteropathy: predisposing factors and treatment.

Cow milk-sensitive enteropathy is a temporary disorder of infancy characterized by a variably abnormal small intestinal mucosa while milk is in the diet. This abnormality is reversed by a cow milk-free diet, only to recur on challenge. Important predisposing factors are age (< 3 years), transient IgA immunodeficiency, atopy, and early bottle feeding. The disorder is diagnosed histologically by evidence of mild-to-moderate partial villous atrophy with thin, often patchy mucosa. For an accurate clinical diagnosis, challenge with the offending food after a demonstrated response to cow milk elimination is critical. When available, serial small intestinal bowel biopsies related to elimination and challenge are also important. Treatment is elimination of cow milk and all foods based on cow milk, and substitution of cow milk feedings with commercially available formulas free of cow milk protein. Five types of cow milk substitutes are described; only nutritionally complete formulas are recommended. Later, a milk challenge will determine the timing of safe reintroduction of cow milk to the diet, at a time when the child is gaining weight, thriving, and symptom free. This dietary treatment is always temporary; reintroduction of a normal diet is nearly always possible between 1 and 2 years of age.

Causality↗
PubMed1992

Neutrophil response to mucosal infection.

Total white cell counts were reviewed in paediatric in-patients with viral gastroenteritis, bacterial gastroenteritis, delayed recovery following acute gastroenteritis, viral lower respiratory tract infections and cow's milk protein intolerance. The prevalence of neutrophilia was not different in the five groups. Neutropenia was common in association with the presence of viruses in stool or sputum, and was significantly more common in these groups than in patients with bacterial gastroenteritis and cow's milk protein intolerance. Neutropenia has not been previously reported in viral gastroenteritis. It was transient in nature and not related to age, sex, weight or antibiotic treatment; no pancreatic disorders were noted.

Bacterial Infections↗
PubMed1992

Dominant role for osmolality in the efficacy of glucose and glycine-containing oral rehydration solutions: studies in a rat model of secretory diarrhoea.

The effect of osmolality on the efficacy of oral rehydration solutions (ORS) and the contribution of the amino acid glycine to water absorption from ORS have been studied in an animal model of secretory diarrhoea. After exposure to pure cholera toxin, rat small intestine (excluding the duodenum) was perfused in situ with seven different ORS. All ORS were derived from a "basic" solution containing Na 50, K 25, Cl 75 and glucose 50 mmol/l to which 25 or 50 mmol/l of glycine, glucose, or mannitol was added. All ORS reversed water secretion to absorption, but maximum water absorption was obtained with the "basic" solution with an osmolality of 200 mOsm/kg. When the osmolality of the "basic" solution was raised to 225 and 250 mOsm/kg by adding mannitol, water absorption decreased. At each of these osmolalities, substitution of mannitol by glycine or glucose resulted in similar increases in water absorption, but all modifications compared unfavourably with the "basic" solution. Net sodium secretion occurred with all ORS tested, despite net water absorption. These findings in a perfusion model of rat small intestine suggest that osmolality is a key factor influencing the efficacy of ORS and that addition of a second substrate, such as glycine, has no beneficial effects. Our results suggest that there is a maximal rate for water absorption from the small intestine which is inversely related to the osmolality of the perfusate.

Animals↗
PubMed1992

The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea.

The value of proximal intestinal mucosal biopsy was reviewed in 381 children presenting with chronic diarrhoea over an eight year period. An enteropathy was detected in 44% of cases and was more frequently seen in those aged less than 6 months. A diagnosis was established in 91% of cases. The most common diagnosis was the postenteritis syndrome where the presence of an enteropathy indicated those requiring treatment with a cows' milk free diet. Other conditions where a biopsy facilitated diagnosis or treatment included giardiasis, enteropathogenic Escheriichia coli, crytosporidiosis, autoimmune enteropathy, and microvillous atrophy. Coeliac disease was considered in 55% of children and established in 8%, clearly identifying those requiring a gluten free diet. This also emphasises the important role of the biopsy procedure in the exclusion of specific diseases. Proximal small intestinal mucosal biopsy is an essential investigation in children with chronic diarrhoea in whom an enteropathy is suspected.

Adolescent↗
PubMed1992

Activation of lamina propria T cells induces crypt epithelial proliferation and goblet cell depletion in cultured human fetal colon.

An organ culture model has been used to study the effects of T cell activation in the human colon. Lamina propria T cells in explant cultures of human fetal colon (11 to 23 weeks gestation) were activated in situ using pokeweed mitogen or an anti-CD3 monoclonal antibody, and compared with unstimulated controls. After three days of culture, there was a two to four-fold increase in crypt epithelial cell proliferation in T cell stimulated explants of more than 15 weeks gestation, associated with a fall in crypt goblet cell numbers of up to 20-fold. By three days, the surface epithelium of stimulated explants appeared thin with loss of goblet cells, and by day 7, severe and extensive mucosal damage was observed by light and electron microscopy. These changes did not occur in control cultures and explants deficient in T cells (less than 16 weeks gestation), and were inhibited by cyclosporin A. These experiments indicate that the increase in epithelial cell proliferation and accompanying goblet cell depletion observed in colorectal crypts in chronic inflammatory bowel disease may be mediated by activated T cells.

Cell Division↗
PubMed1992

Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.

The association between Cryptosporidium, chronic diarrhoea and a proximal small intestinal mucosal enteropathy was reviewed over a six and a half year period. One hundred and twenty three children with cryptosporidiosis and no clinical evidence of immune deficiency were identified. 50% of children excreting only Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea occurred in the first two years of life. A mild to moderate enteropathy was present in all nine children undergoing a small intestinal biopsy and seven showed the presence of Cryptosporidium adhering to villous epithelium. All patients eventually recovered spontaneously. Cryptosporidium is a cause of chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children without immune deficiency. Screening for the parasite should be part of the investigative procedures in children with chronic diarrhoea.

Animals↗
PubMed1991

Gamma/delta T cells and the diagnosis of coeliac disease.

Gamma/delta T cells are increased in the gut epithelium of patients with coeliac disease compared with normal controls. The aim of this study was to determine whether the increase in gamma delta intraepithelial lymphocytes (IEL) is specific for coeliac disease, in which case it could be of diagnostic importance. Biopsies were obtained from children with no intestinal disease, coeliac disease, cow-milk-sensitive enteropathy/post-enteritis syndrome (CMSE PES) and miscellaneous other enteropathies (n = 67). Intraepithelial CD3+ and gamma delta T cells were identified in frozen sections using peroxidase immunohistochemistry. In normal biopsies there were 0-7 gamma delta IEL/100 cells in the epithelium. In untreated coeliac patients this increased to 9-22 gamma delta IEL/100 cells in the epithelium (P = 0.000004). Of 27 patients with morphologic intestinal damage which was not due to coeliac disease, four with CMSE/PES had gamma delta IEL/100 cells in the epithelium in the same range as the patients with coeliac disease. Of these, two had high densities of CD3+ IEL in the epithelium and were indistinguishable from patients with untreated coeliac disease. The other two could be excluded as possible coeliacs because their CD3+ IEL/100 epithelial cells were in the normal range. Thus an increase in gamma delta IEL is not specific for coeliac disease. However, enumeration of both of gamma delta IEL and CD3+ IEL densities will be useful in the exclusion of coeliac disease as a diagnosis in some children.

Adolescent↗
PubMed1991

Search for the ideal oral rehydration solution: studies in a model of secretory diarrhoea.

In situ perfusion of whole rat small intestine was used to compare the efficacy of five oral rehydration solutions in promoting water and sodium absorption in normal intestine and secreting intestine after exposure to cholera toxin. Solutions varied in their sodium (35-90 mmol/l) and glucose (111-200 mmol/l) concentrations, molar ratio of glucose:sodium (1.2-5.8), and osmolality (281-331 mOsmol/kg), and contained either bicarbonate (18-30 mmol/l) or citrate (10 mmol/l). In normal intestine all solutions promoted net water absorption. Cholera toxin induced reproducible water secretion but all solutions reversed this to absorption. Water absorption was greatest with solutions containing sodium 60 mmol/l and glucose 111 or 140 mmol/l, and with a glucose:sodium ratio approximately 2, in both normal and secreting intestine. All solutions promoted net glucose absorption in both normal and secreting intestine. Net sodium absorption occurred with solutions containing greater than or equal to 60 mmol/l sodium in normal intestine but sodium secretion occurred from all solutions in secreting intestine. Sodium movement was directly related to the sodium concentration of the solution and sodium secretion occurred despite net water and glucose absorption. We consider that these studies may guide future development of oral rehydration solutions.

Animals↗
PubMed1991

Response to autoimmune enteropathy to cyclosporin A therapy.

Small bowel enteropathies that are associated with an autoimmune process are often resistant to treatment. Two children with autoimmune enteropathy were treated with cyclosporin A for eight months. Both improved, as assessed by growth, small intestinal mucosal morphology, and carbohydrate absorption. Cyclosporin A is useful in the treatment of autoimmune enteropathy. This report also suggests that T cell activation (which is suppressed by cyclosporin A) is important in the pathogenesis of this condition.

Autoimmune Diseases↗
PubMed1979

Comparison of oral sucrose and glucose electrolyte solutions in the out-patient management of acute gastroenteritis in infancy.

Seventy-three children under the age of 18 months presenting with acute gastroenteritis were given an electrolyte mixture with added sucrose or glucose in a randomized double-blind trial. The time taken to recovery in those sucessfully treated as out-patients was identical. However, of the 34 who received glucose, 11 (32%) required admission compared with 7 (18%) of the 39 who received sucrose. There was a wide range of osmolality of the made-up feeds, indicating inaccuracy in diluting the solutions as prescribed, but this did not in general correlate with need for admission. Sucrose-electrolyte solution is at least as effective as a glucose-electrolyte solution for the out-patient management of acute gastroenteritis in infancy. The cheapness and easy availability of sucrose commends its use in developed and developing countries.

Acute Disease↗
PubMed1979

The structure of the enterocyte in relation to its position on the villus in childhood: an electron microscopical study.

An electron study of histologically normal small intestinal mucosa taken from 10 children has shown, on morphological grounds, that the mid-region of the villus is best adapted for digestion and absorption. Microvilli in the mid-region were tallest, and presented the maximal surface area. In contrast the upper region of the villus exhibited a reduction in microvillous surface area and some cellular damage. Cellular extrusion was observed near the base of the villus as well as near the tip. The occurrence of cellular alterations in the oldest and more exposed regions of normal mucosa in childhood may be symptomatic of a natural epithelial ageing process but may also be the result of an adverse luminal effect on the enterocytes. These findings differ from some of the observations made on adult small intestinal mucosa where it has been reported that the microvilli present a maximal surface area and the enterocytes are most active at the tips of the villi rather than in the mid-region.

Child, Preschool↗
PubMed1979

The diagnosis of coeliac disease. A commentary on the current practices of members of the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN).

In 1977, 53 members of ESPGAN completed a questionnaire on their current practice in diagnosing coeliac disease. The usefulness of the 'Interlaken' criteria enumerated 9 years previously was reassessed. Details were obtained about the initial diagnostic approach, the acceptable histological criteria of the initial jejunal biopsy, and the timing, technique, response, and interpretation of early and late rechallenges with gluten. Answers indicated that, although the initial mucosal lesion is usually 'flat' at the time of diagnosis, a few infants may present at a time when the mucosal lesion is less completely damaged. Furthermore, the degree of histological change after gluten challenge that is acceptable as a positive response may vary according to the state of the mucosa before challenge. It was noted that there are still no generally agreed criteria by which the histological lesions may be described, so that (after further discussions at the Third International Coeliac Conference in Galway) a European panel has been set up to make recommendations. In the experience of ESPGAN members, most coeliac children will have a histological relapse within 2 years of reintroduction of gluten. But a small number of unorthodox cases were reported that suggest that (a) histological relapse may take longer than 2 years to appear, or (b) the degree of sensitivity to gluten may vary at different ages. Very long-term follow-up will be needed to explain these anomalies. Meanwhile the search continues for 'the basic defect'.

Age Factors↗